Formaldehyde → 1-[(3-{2-[3-Cyano-4-(2-methylpropyl)phenyl]-1,3-thiazol-5-yl}-2-ethylphenyl)methyl]-4-piperidinecarboxylic acid

HRID 1942747ノート

反応式

HRID 1942747 の反応式
[CH2:1]([C:3]1[C:8]([CH:9]=O)=[CH:7][CH:6]=[CH:5][C:4]=1[C:11]1[S:15][C:14]([C:16]2[CH:17]=[CH:18][C:19]([CH2:24][CH:25]([CH3:27])[CH3:26])=[C:20]([CH:23]=2)[C:21]#[N:22])=[N:13][CH:12]=1)[CH3:2].[NH:28]1[CH2:33][CH2:32][CH:31]([C:34]([O:36]CC)=[O:35])[CH2:30][CH2:29]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C=O>ClCCl.C(O)(=O)C>[C:21]([C:20]1[CH:23]=[C:16]([C:14]2[S:15][C:11]([C:4]3[C:3]([CH2:1][CH3:2])=[C:8]([CH2:9][N:28]4[CH2:29][CH2:30][CH:31]([C:34]([OH:36])=[O:35])[CH2:32][CH2:33]4)[CH:7]=[CH:6][CH:5]=3)=[CH:12][N:13]=2)[CH:17]=[CH:18][C:19]=1[CH2:24][CH:25]([CH3:27])[CH3:26])#[N:22]

参加物

7

反応物 4

HCID 712FormaldehydeHCID 70770Ethyl 4-piperidinecarboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 866590095-[5-(2-Ethyl-3-formylphenyl)-1,3-thiazol-2-yl]-2-(2-methylpropyl)benzonitrile

生成物 1

HCID 545771581-[(3-{2-[3-Cyano-4-(2-methylpropyl)phenyl]-1,3-thiazol-5-yl}-2-ethylphenyl)methyl]-4-piperidinecarboxylic acid収率 20.5%

試薬・触媒・溶媒 2

HCID 176Acetic Acid溶媒HCID 6344Dichloromethane溶媒

実験手順

A solution of 5-[5-(2-ethyl-3-formylphenyl)-1,3-thiazol-2-yl]-2-(2-methylpropyl)benzonitrile (D92) (150 mg), ethyl 4-piperidinecarboxylate (63.0 mg) and acetic acid (0.1 mL) in dichloromethane (DCM) (10 mL) was stirred at room temperature for 15 min, then sodium triacetoxyborohydride (255 mg) was added. The mixture was stirred at room temperature for 2 h, then formaldehyde (0.11 mL) was added. The mixture was stirred at room temperature overnight. After concentration, the residue was partitioned between ethyl acetate and water, washed with saturated brine. The organic phase was collected and evaporated, the residue was dissolved in DMF (5 mL) and 2M NaOH (2 mL) solution was added. The mixture was stirred at 50° C. for 1 h, then cooled to room temperature. This reaction mixture was acidified with 2M HCl to pH 5-6, extracted with ethyl acetate for three times. The combined organic phase was concentrated and the residue purified by Mass Directed AutoPrep to afford 1-[(3-{2-[3-cyano-4-(2-methylpropyl)phenyl]-1,3-thiazol-5-yl}-2-ethylphenyl)methyl]-4-piperidinecarboxylic acid (E42) (40 mg) as a TFA salt. δH (DMSO-d6, 400 MHz): 0.92 (6H, d), 1.02 (3H, t), 1.78 (2H, m), 1.98 (2H, m), 2.07 (2H, m), 2.73 (2H, d), 2.83 (2H, m), 3.19 (2H, m), 3.46 (2H, m), 4.41 (2H, m), 7.48 (2H, t), 7.63 (2H, m), 7.96 (1H, s), 8.22 (1H, dd), 8.35 (1H, d), 9.23 (1H, br s), 12.58 (1H, br s). δF (DMSO-d6, 376 MHz): −74.2. MS (ES): C29H33N3O2S requires 487. found 488.3 (M+H+).

後処理

  1. stirringThe mixture was stirred at room temperature overnight
  2. concentrationAfter concentration
  3. customthe residue was partitioned between ethyl acetate and water
  4. washwashed with saturated brine
  5. customThe organic phase was collected
  6. customevaporated
  7. dissolutionthe residue was dissolved in DMF (5 mL)
  8. addition2M NaOH (2 mL) solution was added
  9. stirringThe mixture was stirred at 50° C. for 1 h
  10. temperaturecooled to room temperature
  11. extractionextracted with ethyl acetate for three times
  12. concentrationThe combined organic phase was concentrated
  13. customthe residue purified by Mass Directed AutoPrep

出典と根拠

ORDレコード
ord-7ed7befd50ad4385a3caae640f038158
出典データセット
uspto-grants-2013_03
特許番号
US08389508B2

反応ノート

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